Development of Multipotent Adult Progenitor Cells for Treatment of Multiple Sclerosis

Background: Stem cell therapies are currently being investigated as potential therapeutic treatments for autoimmune disorders such as multiple sclerosis (MS). However, the mechanistic interaction between the diseased tissue environment and transplanted cells is often poorly understood, leading to inefficient or inappropriate applications of cell therapies that may not   afford significant health benefits.

Objectives: We are investigating the potential use of human Multipotent Adult Progenitor Cells (MAPC; MultiStem®) as a cellular therapeutic for the treatment of MS.  We describe experiments designed to evaluate efficacy, dose, window of therapeutic benefit, and effects upon remyelination.

Methods: Experimental allergic encephalomyelitis (EAE) was induced in C57Bl/6 mice.  Efficacy was examined after administering 1, 3, or 9 million cells intravenously (IV), compared to control animals administered vehicle. Cells or vehicle were administered after significant symptom onset, and behavior was monitored for 28 days by a blinded observer.  Window of therapeutic benefit was examined by administering 1 million cells IV at different timepoints in the course of disease.  Myelin content was examined via luxol fast blue (LFB) staining and electron microscopy (EM).  Investigation of the direct effects of MAPC upon remyelination was achieved via direct injection of cells or vehicle into lysolecithin (LPC) lesions in adult rat spinal cords.  Lesions were characterized via LFB staining and immunocytochemistry. 

Results: Significant and sustained behavioral improvement was observed in response to all cell doses tested, when administered after symptom onset.  Presymptomatic treatment did not prevent disease onset.  Examination of myelination status demonstrated decreased average area of demyelinated lesions in spinal cords of cell-treated animals, as well as a significant decrease in the number of complete lesions.  Further analysis via EM showed abundant evidence of newly remyelinated axons within cell-treated animals.  Subsequent studies in LPC-lesioned rat spinal cords demonstrated increased remyelination in cell-treated lesions associated with significant induction of M2 macrophages in the core of the lesion. 

Conclusions: The results of these studies suggest that treatment of MS patients with MultiStem may provide clinical benefit through modulation of immune status and promotion of remyelination. Funded through collaboration with Fast Forward LLC and National MS Society.